The long term goal of this laboratory is to establish the functional neuroanatomy of the central and peripheral neural control systems that regulate feeding, energy metabolism and body weight. The proposed research will identify some of the crucial neural substrate that links the brain to the abdominal visceral organs. The aim is to morphologically, histochemically and functionally characterize the vagal and spinal sensory innervation of the gastrointestinal tract, liver and pancreas. The methodology will make use of recent developments in anterograde neural tracing and staining with fluorescent probes, and optical sectioning by means of laser scanning confocal microscopy. First, the viscerotropic innervation territories and distribution patterns at the gross anatomical level, the branching and collateralization patterns of individual afferent fibers within specialized regions such as the glandular stomach, duodenum and jejunum, and the fine structure of terminal specializations will be assessed. Second, the histochemical and immunocytochemical character of the cellular environment of vagal and spinal afferent terminals will be determined in order to shed light on the possible mechanisms of signal transduction at the receptor sites. Third, we will identify in the brainstem and spinal cord the second order neurons that are physiologically activated through functionally specific primary afferents. Together these analyses will help establish a functional anatomy of visceral afferents and efferents innervating areas that play key roles in the detection of nutrients, nutrient related hormonal signals, toxins and immunogenic substances. These new insights will have direct relevance for clinical issues such as eating disorders, obesity, irritable bowel syndrome, gastric and duodenal ulcer, food allergies and parasitic infections.